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INTRODUCTION TO PROTEINPROTEIN INTERACTION PRATIK DUTTA, 1621CS05, AINLPML Group, CSE Dept, IIT PATNA Guidance By: Dr. Sriparna Saha OUTLINE OF THE PRESENTATION What is Protein?? Protein Structure RNA/DNA/ Gene/ Protein Central Dogma of Biology Microarray and Gene Expression Data Proteinprotein Interaction Protein Interaction Network Conclusion 2 AINLPML GROUP, IIT PATNA 08/02/17 WHAT IS PROTEIN Protein are large biomolecules that consisting of one or more long chains of amino acids A protein contains at least one long polypeptide( chain of amino acids) Primarily the sequence of amino acid differs the protein from each other 3D structure of protein myoglobin 3 AINLPML GROUP, IIT PATNA 08/02/17 AMINOACIDS AND POLYPEPTIDE Amino acid are biologically important organic compound that consists of Amine group( NH2) Carboxylic Acid group (COOH) and a side chain( R) Carboxylic group Amine group Structure of an αamino acid Therefore the key elements of amino acid are carbon (C) , hydrogen(H) , oxygen(O) and nitrogen(N) † AINLPML GROUP, IIT PATNA † 08/02/17 4 AMINOACIDS AND POLYPEPTIDE Though there are about 500 amino acids, only 20 amino acid appear in genetic code When two or more amino acid is connected through peptide bond it is called polypeptide(amino acid chain) 5 † AINLPML GROUP, IIT PATNA † 08/02/17 STRUCTURAL ELEMENTS OF PROTEIN Key elements of protein 3d structure of protein Molecular structure of amino acid chain of Amino acid Molecular structure of peptide † AINLPML GROUP, IIT PATNA † 08/02/17 6 PROTEIN STRUCTURE Protein structure is the threedimensional arrangement of atoms in a protein molecule To perform several biological functions, protein folds into one or more specific spatial conformations Several noncovalent interactions are responsible for this confirmations Levels of protein structure Primary structure: linear sequence of amino acids in the polypeptide chain Secondary structure : helical structure due to hydrogen bond between the mainchain peptide groups. E.g αhelix and βsheets Tertiary structure: folded into a compact globular structure due to hydrophobic interactions 7 † AINLPML GROUP, IIT PATNA † 08/02/17 THE CENTRAL DOGMA Relation between DNA, RNA and proteins † AINLPML GROUP, IIT PATNA † CENTRAL DOGMA Explains the flow of genetic information from DNA to RNA, to make a functional product Protein Stages of Central Dogma Replication: Fundamental step of central dogma, make a new DNA from existing DNA by DNA polymerase Transcription: Make new mRNA from DNA by RNA polymerase Translation: Make new protein from mRNA by ribosome 9 † AINLPML GROUP, IIT PATNA † 08/02/17 CENTRAL DOGMA Transcription Translation Central Dogma of Molecular Biology † AINLPML GROUP, IIT PATNA † 08/02/17 10 GENE EXPRESSION VALUES † AINLPML GROUP, IIT PATNA † GENE EXPRESSION VALUE In the field of molecular biology, gene expression profiling is the measurement of the activity of thousands of genes at once Gene expression values of large genes are measured by microarray Gene expression can be quantified by measuring either mRNA or protein Gene Expression Measurement Method Single Channel Arrays: Give estimations of the absolute levels of gene expression compare two set of condition for each gene requires two separate singledye hybridizations Two Channel Arrays: Two hybridized cDNA samples (e.g. diseased tissue versus healthy tissue) and labelled with two different fluorescentdyes(Cy5 and Cy3) 12 † AINLPML GROUP, IIT PATNA † 08/02/17 GENE EXPRESSION VALUE 13 † AINLPML GROUP, IIT PATNA † 08/02/17 GENE EXPRESSION DATASET ( http://www.ncbi.nlm.nih.gov/sites/GDSbrowser?acc=GDS1388 ) Gene expression level of gene i in mRNA sample j Single Channel Arrays: (normalized) Log2(Intensity) Intensity (Cy 5) Double Channel Arrays: log 2 Intensity (Cy 3) 14 † AINLPML GROUP, IIT PATNA † 08/02/17 PROTEINPROTEIN INTERACTION † AINLPML GROUP, IIT PATNA † PROTEINPROTEIN INTERACTION Lasting and specific physical contacts established between two or more proteins for carried out some specific biological activity Represents pair wise protein interactions of the organisms Example of PPI Muscle Contraction Cellular Transportation protein1 protein2 Proteinprotein Interaction † AINLPML GROUP, IIT PATNA † 08/02/17 16 PROTEINPROTEIN INTERACTION Interaction between two proteins is carried out by several biochemical events Electrostatic Forces: Force interacting between static electrically charged particles Hydrogen bonds: electrostatic attraction between hydrogen(H) and highly electronegative atom(e.g. O, N) Van der Waals forces: residual attractive or repulsive forces between molecules or atomic groups Hydrophobic interactions: Maximize hydrogen bond 17 † AINLPML GROUP, IIT PATNA † 08/02/17 TYPES OF INTERACTION Stability Structural Stable: Always stable and active e.g. Hormones, Hemoglobin Transient: Control the majority of cellular processes, can be strong or weak, fast or slow Homooligomer : Same type of subunits e.g. Enzymes Heterooligomer: Different types of subunits e.g. Gproteins Chemical Bonding Covalent Bonding: Share electron pairs Noncovalent Bonding: Rather sharing electrons , involves in some electromagnetic forces 18 † AINLPML GROUP, IIT PATNA † 08/02/17 IMPORTANCE OF PPI NETWORK Useful for isolating groups of interacting proteins that participate in the same biological process Helps to understand the mechanism of regulating cell life Useful to predict the biological functions of uncharacterized proteins 19 † AINLPML GROUP, IIT PATNA † 08/02/17 REFERENCES http://www.medicalnewstoday.com/articles/196279.php http://www.chemistry.uoguelph.ca/educmat/phy456/456lec02.htm http://www.biology.arizona.edu/biochemistry/problem_sets/aa/aliph atic.html http://www.particlesciences.com/news/technicalbriefs/2009/protein structure.html http://www.slideshare.net/NaghmehPoorinmohamma/proteinprotein interactionppi http://www.clearbiology.com/biochemistryreviewactivity/proteins/ http://worldofbiochemistry.blogspot.in/2013_09_01_archive.html http://www.ch.embnet.org/CoursEMBnet/Pages3D07/documents/3Di ntro07.pdf 20 http://www.ch.embnet.org/CoursEMBnet/PagesTR08/slides/EmbNe t_CleanEx_1.pdf † AINLPML GROUP, IIT PATNA † 08/02/17 https://en.wikipedia.org/wiki THANK YOU 21 † AINLPML GROUP, IIT PATNA † 08/02/17